# Project 2-Metabolic Modulation of Myeloid-Derived Suppressor Cells to Increase Efficacy of Neo adjuvant Chemotherapy and Immunotherapy

> **NIH NIH P20** · LSU HEALTH SCIENCES CENTER · 2020 · $270,954

## Abstract

ABSTRACT
The incidence of triple negative breast cancer (TNBC) in African American (AA) women in Louisiana is
approximately double that of European America (EA) women. The advanced stage at presentation, the
absence of hormonal receptors and the poor response to neoadjuvant chemotherapy negatively impact the
outcome for these patients and further worsens the health disparity of this disease. Therefore identifying
approaches that improve the efficacy of neoadjuvant chemotherapy or novel immunotherapies may improve
survival in these patients, and could in part start to address this inequality. Chronic inflammatory myeloid cells
in the tumor microenvironment, represented by myeloid derived suppressor cells (MDSC) impair the efficacy of
chemotherapy, radiation therapy and immunotherapy. Previous approaches to deplete MDSC using
chemotherapy or tyrosine kinase inhibitors have been shown to enhance the therapeutic efficacy of
chemotherapy and immunotherapy. However these approaches have only short term lived effects. Our data
instead show that MDSC are dependent on lipid metabolism to support their functions, including the production
of arginase I, their primary immunosuppressive mechanism. Blocking fatty acid oxidation or arginase I inhibits
the function of MDSC, and significantly potentiates the efficacy of chemotherapy and immunotherapy. Our data
show that this can be achieved with repurposed drugs or with novel arginase I inhibitors. Project 2 will
demonstrate that MDSC infiltrating human TNBC tumors are dependent on lipid metabolism and will determine
if they are sensitive to inhibitors of these pathways. Similarly, using murine models of TNBC, we will test if the
inhibitors of lipid metabolism or arginase I have a synergistic therapeutic effect when combined with
chemotherapy or immunotherapy. The availability of the specific lipid metabolism and arginase I inhibitors
makes the proposed research even more significant since it facilitates the development of clinical trials for a
future SPORE application.

## Key facts

- **NIH application ID:** 10005254
- **Project number:** 5P20CA233374-03
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** AUGUSTO C. OCHOA
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $270,954
- **Award type:** 5
- **Project period:** 2018-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005254

## Citation

> US National Institutes of Health, RePORTER application 10005254, Project 2-Metabolic Modulation of Myeloid-Derived Suppressor Cells to Increase Efficacy of Neo adjuvant Chemotherapy and Immunotherapy (5P20CA233374-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10005254. Licensed CC0.

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